EFFECTS OF 3,4-DIHYDRO-8-(2-HYDROXY-3-ISOPROPYLAMINO-PROPOXY)-3-NITROXY-2H-1-BENZOPYRAN (K-351) ON SMOOTH-MUSCLE CELLS AND NEUROMUSCULAR-TRANSMISSION IN GUINEA-PIG VASCULAR TISSUES

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (2) , 560-572
Abstract
The effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-benzopyran (K-351) on vascular smooth muscle cells and neuromuscular transmission were investigated by the microelectrode and mechanographic methods using intact and skinned smooth muscles from guinea pigs. K-351 markedly inhibited the norepinephrine-induced contraction and slightly reduced the K-induced contraction in the mesenteric artery, but did not affect the acetylcholine-induced contraction in the coronary artery. K-351 inhibited the contraction evoked by perivascular nerve stimulation to a greater extent than that evoked by exogenously applied norepinephrine in the pulmonary artery. These sequences were reversed in the mesenteric artery. In the mesenteric artery, K-351 (6 .times. 10-7 M) suppressed and phentolamine (10-6 M) enhanced the contraction evoked by perivascular nerve stimulation, at frequencies > 1.0 Hz. In the mesenteric artery, K-351 did not affect the spike evoked by an outward current pulse or the spike of the excitatory junction potential; in the portal vein, it increased spontaneously generated spikes due to membrane depolarization. In the skinned mesenteric artery, K-351 did not modify the amplitude of Ca-induced contraction. The excitatory junction potential evoked by perivascular nerve stimulation (0.1-1.0 Hz) was markedly inhibited by K-351 with no effect on the facilitation process, whereas phentolamine enhanced both excitatory junction potentials and the facilitation process. K-351 inhibited mainly intra- and extrajunctional .alpha.-adreneoceptors and, as the former was not affected by phentolamine or prazosin, the action of this new agent differs from the actions of previously available .alpha.-1 and .alpha.-2 adrenoceptor antagonists.